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Purpose: This study aimed to investigate the prevalence and co-prevalence of comorbidities among Chinese individuals with type 2 diabetes (T2DM). Methods: Medical records were retrospectively retrieved from the 3B Study database, which provided a comprehensive assessment of comorbid conditions in Chinese adult outpatients with T2DM. Patient characteristics, laboratory measures, and comorbidities were summarized via descriptive analyses, overall and by subgroups of age (<65, 65-74, 75 years) and gender. Results: Among 25,454 eligible patients, 53% were female, and the median age was 63 years. The median time of diabetes duration was 6.18 years. A total of 20,309 (79.8%) patients had at least one comorbid condition alongside T2DM. The prevalence of patients with one, two, three, and four or more comorbid conditions was 28.0%, 24.6%, 15.6%, and 11.6%, respectively. Comorbidity burden increased with longer T2DM duration. Older age groups also exhibited higher comorbidity burden. Females with T2DM had a higher overall percentage of comorbidities compared to males (42.7% vs. 37.1%). The most common comorbid conditions in T2DM patients were hypertension (HTN) in 59.9%, overweight/obesity in 58.3%, hyperlipidemia in 42.0%, retinopathy in 16.5%, neuropathy in 15.2%, cardiovascular disease (CVD) in 14.9%, and renal disease in 14.4%. The highest co-prevalence was observed for overweight/obesity and HTN (37.6%), followed by HTN and hyperlipidemia (29.8%), overweight/obesity and hyperlipidemia (27.3%), HTN and CVD (12.6%), HTN and retinopathy (12.1%), and HTN and renal disease (11.3%). Conclusion: The majority of T2DM patients exhibit multiple comorbidities. Considering the presence of multimorbidity is crucial in clinical decision-making. Systematic review registration: https://clinicaltrials.gov/, identifier NCT01128205.
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Comorbilidad , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Prevalencia , Estudios Transversales , China/epidemiología , Adulto , Bases de Datos Factuales , Hipertensión/epidemiología , Hipertensión/complicaciones , Pueblos del Este de AsiaRESUMEN
BACKGROUND: To compare glycemic control in Chinese patients with type 2 diabetes mellitus (T2DM) whose blood glucose levels were inadequately controlled with oral antidiabetic drugs after beinaglutide alone or combined with insulin glargine (IGlar). METHODS: In this 16-week multicenter, randomized clinical trial, 68 participants randomly received beinaglutide or IGlar for 8 weeks, then the two drugs in combination for 8 weeks. The primary outcomes were the proportion of individuals achieving their glycemic target and the change in glucose variability as measured with a continuous glucose monitoring system from baseline to 8 and 16 weeks. RESULTS: Both the beinaglutide and IGlar groups showed increased proportions achieving their glycemic target at 8 weeks, and the combination augmented the proportion reaching the glycated hemoglobin target from 25.42% at 8 weeks to 40.68% at 16 weeks. The beinaglutide group showed a significant reduction in body weight, body mass index, waist circumference, and systolic blood pressure. Beinaglutide elevated high-density lipoprotein cholesterol by 0.08 mmol/L (95% confidence interval [CI], 0.00-0.16), and diminished low-density lipoprotein cholesterol by 0.21 mmol/L (95% CI, 0.05-0.48), whereas IGlar showed no effect. Though IGlar was more efficient in lowering fasting plasma glucose than beinaglutide at comparable efficacies (to -1.57 mmol/L [95% CI, -2.60 to -0.54]), this difference was abolished in patients whose fasting C-peptide was ≥0.9 ng/mL. CONCLUSION: Beinaglutide exhibited a favorable hypoglycemic effect on patients with T2DM, and in combination with IGlar, glucose level was further decreased. Low fasting C-peptide in patients may reduce the glycemic response to beinaglutide therapy. We recommend that C-peptide levels be evaluated when using or switching to the novel glucagon-like peptide-1 receptor agonists beinaglutide. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03829891.
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OBJECTIVES: To explore the relationship between serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) ratio (UHR) and metabolic syndrome (MetS) in nondiabetic individuals. METHODS: A total of 15,760 nondiabetic participants were screened from the China National Diabetes and Metabolic Disorders Study. Pearson correlation was used to determine the correlation between the components of MetS and UHR, HDL-C, and UA. Receiver operating characteristic curves were used to evaluate the ability of UHR, HDL-C, and UA to identify MetS in the nondiabetic population. RESULTS: A total of 6,386 men and 9,374 women were enrolled in this study. There were 1,480 (23.2%) men and 1,828 (19.5%) women with MetS. UHR significantly correlated with the components of MetS in men and women, especially with waist circumference and triglyceride. In men, although HDL-C showed a higher specificity index, UHR presented higher sensitivity index and area under the curve (AUC) than HDL-C (P = 0.0001) and UA (P < 0.0001), with AUC (95% CI) of 0.762 (0.752-0.773). Higher AUCs of UHR relative to HDL-C and UA were also observed in the age groups <40 and 40-59 years. There was no significant difference in AUC between UHR and HDL-C in the age group ≥60 years (P = 0.370). However, similar results were not observed in women. CONCLUSION: UHR significantly correlated with the components of MetS and could serve as a novel and reliable marker for identifying the population at a high risk of MetS in nondiabetic men, especially in younger adults.
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HDL-Colesterol , Síndrome Metabólico , Ácido Úrico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , HDL-Colesterol/sangre , Diabetes Mellitus/sangre , Pueblos del Este de Asia , Síndrome Metabólico/sangre , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Ácido Úrico/sangreRESUMEN
OBJECTIVE: To investigate the knowledge and practices of diabetes drug injection techniques of diabetes patients, nurses, and physicians to support formulating national guidelines for standardized diabetes drug injection techniques. PATIENTS AND METHODS: In this nationwide multicenter cross-sectional survey conducted between November and December 2020, patients, nurses, and physicians were randomly chosen from 250 primary, 150 secondary, and 100 tertiary care hospitals using the stratified cluster sampling method. Their knowledge and/or practices of diabetes drug injection techniques were surveyed using the Diabetes Drug Injection Knowledge and Practice Questionnaire for Physicians, Nurses, and Patients. RESULTS: In total, 10,694, 2643, and 2816 eligible questionnaires were collected from patients, physicians, and nurses, respectively. Overall, 78.2% (7588/9709) type 2 diabetes patients failed to attain the target hemoglobin A1c. Hypoglycemic episodes and lipohypertrophy occurred in 19.8% and 34.7% of the patients, respectively. Needle reuse (odds ratio, 1.19; 95% CI, 1.07 to 1.33) and incorrect injection site rotation (odds ratio, 1.32; 95% CI, 1.16 to 1.51) were associated with failure to attain the target hemoglobin A1c. Overall, 48.9% physicians and 20.4% nurses had a poor knowledge domain score. Care setting and training, diabetes care experience, and regions were significant determinants of diabetes drug injection knowledge domain scores in both physicians and nurses. CONCLUSION: Poor glycemic control, occurrences of injection-associated complications in diabetes patients, and poor knowledge domain scores of a subset of physicians and nurses highlight the importance of regular assessment and education regarding diabetes drug injection techniques for physicians and nurses and development of national guidelines for diabetes drug injection. TRIAL REGISTRATION: Chictr.org.cn (ChiCTR2100045302).
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The current epidemic status of diabetic retinopathy in China is unclear. A national prevalence survey of diabetic complications was conducted. 50,564 participants with gradable non-mydriatic fundus photographs were enrolled. The prevalence rates (95% confidence intervals) of diabetic retinopathy and vision-threatening diabetic retinopathy were 16.3% (15.3%-17.2%) and 3.2% (2.9%-3.5%), significantly higher in the northern than in the southern regions. The differences in prevalence between those who had not attained a given metabolic goal and those who had were more pronounced for Hemoglobin A1c than for blood pressure and low-density lipoprotein cholesterol. The participants with vision-threatening diabetic retinopathy had significantly higher proportions of visual impairment and blindness than those with non-vision-threatening diabetic retinopathy. The likelihoods of diabetic retinopathy and vision-threatening diabetic retinopathy were also associated with education levels, household income, and multiple dietary intakes. Here, we show multi-level factors associated with the presence and the severity of diabetic retinopathy.
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Diabetes Mellitus , Retinopatía Diabética , Adulto , Humanos , Retinopatía Diabética/epidemiología , Prevalencia , Factores de Riesgo , Hemoglobina Glucada , China/epidemiologíaRESUMEN
AIMS: To assess the prevalence of diabetic peripheral neuropathy (DPN) and its risk factors in the type 2 diabetes mellitus (T2DM) population. METHODS: This cross-sectional study enroled patients with T2DM between July and December 2017 from 24 provinces in China. Diabetic peripheral neuropathy and its severity were assessed by the Toronto clinical scoring system, neuropathy symptoms score (NSS) and neuropathy disability score. The prevalence of DPN and its risk factors were analysed. RESULTS: A total of 14,908 patients with T2DM were enroled. The prevalence of DPN was 67.6%. Among 10,084 patients with DPN, 4808 (47.7%), 3325 (33.0%), and 1951 (19.3%) had mild, moderate, and severe DPN, respectively. The prevalence of DPN in females was higher than in males (69.0% vs. 66.6%, P = 0.002). The prevalence of DPN increased with age and course of diabetes and decreased with body mass index (BMI) and education level (all P for trend <0.05). The comorbidities and complications in patients with DPN were higher than in those without DPN, including hypertension, myocardial infarction, diabetic retinopathy, and diabetic nephropathy (all P < 0.001). Age, hypertension, duration of diabetes, diabetic retinopathy, diabetic nephropathy, glycated haemoglobin, high-density lipoprotein cholesterol, and lower estimated glomerular filtration rate were positively associated with DPN, while BMI, education level, fasting C-peptide, and uric acid were negatively associated with DPN. CONCLUSIONS: Among patients with T2DM in China, the prevalence of DPN is high, especially in the elderly, low-income, and undereducated patients.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Neuropatías Diabéticas , Retinopatía Diabética , Hipertensión , Masculino , Femenino , Humanos , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Estudios Transversales , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/complicaciones , Prevalencia , Factores de Riesgo , Hipertensión/complicaciones , Nefropatías Diabéticas/diagnósticoRESUMEN
AIM: The study aimed to assess the prevalence and risk factors of painful diabetic peripheral neuropathy (PDPN) in patients with type 2 diabetes mellitus (T2DM) and diabetic peripheral neuropathy (DPN) in mainland China. METHODS: This nationwide cross-sectional study enrolled T2DM patients with DPN from 25 provinces in China between July 2017 and December 2017. The prevalence, characteristics, and risk factors of PDPN were analyzed. RESULTS: Among 25,710 patients with T2DM and DPN, 14,699 (57.2%) had PDPN. The median age was 63 years old. Age over 40 years old, education level, hypertension, myocardial infarction, duration of diabetes of over five years, diabetic retinopathy and nephropathy, moderate total cholesterol, moderate and higher low-density lipoprotein (LDL) increased uric acid (UA) and decreased estimated glomerular filtration rate (eGFR) were independently associated with PDPN (all P < 0.05). Compared with low levels of C-peptide, moderate levels were independently associated with a higher risk of PDPN, while high levels were associated with a lower risk (all P < 0.001). CONCLUSIONS: In mainland China, more than half of the patients with DPN have neuropathic pain. Patients with older age, lower education level, longer duration of diabetes, lower LDL, increased UA, decreased eGFR, and comorbidities had an increased risk of PDPN.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Neuralgia , Adulto , Humanos , Persona de Mediana Edad , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Neuropatías Diabéticas/epidemiología , Neuralgia/epidemiología , Prevalencia , China/epidemiologíaRESUMEN
AIMS: This study investigated insulinoma-associated-2 autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies' association with clinical characteristics and HLA-DR-DQ genes. MATERIALS AND METHODS: This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency. RESULTS: IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD. CONCLUSIONS: IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.
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Proteínas de Transporte de Catión , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Insulinoma , Neoplasias Pancreáticas , Humanos , Diabetes Mellitus Tipo 1/genética , Transportador 8 de Zinc , Autoanticuerpos , Estudios Transversales , Péptido C , Hemoglobina Glucada , Proteínas de Transporte de Catión/genética , Antígenos HLA-DR , Glutamato DescarboxilasaRESUMEN
DACH1 is an important component of the retinal determinate gene network (RDGN), which regulates the expression of target genes by directly binding or interacting with other factors. DACH1 shows inhibitory effects in most tumors, but its role in papillary thyroid carcinoma is unclear and warrants further investigation. We assessed the expression of DACH1 in different tissues and correlation with immune infiltration by The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMMER2.0 databases). The effects of DACH1 on the proliferation and migration of TPC-1 and Bcpap cells were assessed by cell viability assay, colony formation assay, wound healing assay, transwell migration assay, and flow cytometry. Finally, the effects of DACH1 on CXCL8, CXCL10, and CXCL12 expression in Nthy-ori-3-1, TPC-1 and Bcpap cells were assessed by enzyme-linked immunosorbent assay kit and real-time polymerase chain reaction, respectively. The results showed that DACH1 was differentially expressed in different tumors and tissues. Basal expression of DACH1 was lower in thyroid and papillary thyroid carcinoma than in other normal tissues and corresponding tumors, and positively correlated with CD8+ T cell infiltration. In Nthy-ori-3-1, TPC-1 and Bcpap cells, overexpression of DACH1 inhibited cell migration and proliferation, and the opposite results was obtained by knocking down DACH1 using small interfering RNA. We also demonstrated that DACH1 regulated chemokines CXCL8, CXCL10, and CXCL12, thereby modulating tumor immunity.
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Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Proteínas del Ojo/genética , Factores de TranscripciónRESUMEN
BACKGROUND: Fasting glucose variability (FGV) extensively promotes the onset and development of diabetic complications. This study aimed to evaluate the FGV in type 2 diabetes mellitus (T2DM) patients administered basal insulin using a needle-free insulin injector (NFII). RESEARCH DESIGN AND METHODS: This was a prospective randomized multicenter open-label crossover study. We randomly assigned 48 T2DM patients to receive basal insulin by NFII or conventional insulin pen (CIP) for 7-14 days and were then crossed over after washout. We conducted continuous glucose monitoring to investigate the FGV, our primary outcome was a composite parameter of the FGV with a fasting blood glucose target between 4.4 and 6.1 mmol/L. RESULTS: The coefficient of variation for sensor glucose at 6 a.m. with CIP was 11.67 (8.70,14.81)% vs. 9.48 (6.48,12.24)% with NFII (p = 0.003), and the coefficient of variation for mean sensor glucose at 5-6 a.m. with CIP was 12.70 (9.17,16.56)% vs. 9.23 (7.01,11.98)% with NFII (p < 0.001). The overall basal insulin dosage with CIP injection was 18.00 (16.00, 20.00) IU vs. 16.00 (12.00, 19.00) IU during NFII (p < 0.003). CONCLUSION: Compared with CIP, the use of the NFII to inject basal insulin improved FGV in T2DM. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn Identifier is ChiCTR2000034674.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucemia , Hipoglucemiantes/uso terapéutico , Estudios Cruzados , Automonitorización de la Glucosa Sanguínea , Glucosa , Estudios Prospectivos , Insulina/uso terapéutico , AyunoRESUMEN
Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy (trastuzumab), cancer stem cell (CSC)-like properties and multiple chemoresistance often concur and intersect in breast cancer, but molecular links that may serve as effective therapeutic targets remain largely unknown. Here, we identified the long noncoding RNA, LINC00589 as a key regulatory node for concurrent intervention of these processes in breast cancer cells in vitro and in vivo. We demonstrated that the expression of LINC00589 is clinically valuable as an independent prognostic factor for discriminating trastuzumab responders. Mechanistically, LINC00589 serves as a ceRNA platform that simultaneously sponges miR-100 and miR-452 and relieves their repression of tumor suppressors, including discs large homolog 5 (DLG5) and PR/SET domain 16 (PRDM16, a transcription suppressor of mucin4), thereby exerting multiple cancer inhibitory functions and counteracting drug resistance. Collectively, our results disclose two LINC00589-initiated ceRNA networks, the LINC00589-miR-100-DLG5 and LINC00589-miR-452-PRDM16- mucin4 axes, which regulate trastuzumab resistance, CSC-like properties and multiple chemoresistance of breast cancer, thus providing potential diagnostic and prognostic markers and therapeutic targets for HER2-positive breast cancer.
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Background: A high seropositive rate of thyroid autoantibodies is often reported in patients with type 1 diabetes mellitus (T1DM), latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus (T2DM). However, the positive rate of thyroid autoantibodies in latent autoimmune diabetes in youth (LADY) patients has not been reported in China. Thus, the purpose of the current study was to clarify the thyroid autoantibody distribution in patients with LADY to provide evidence for the clinical screening of autoimmune thyroid diseases (AITD). Methods: This nationwide, multicenter and cross-sectional study included 1,723 younger patients (<30 years old) and 2,000 older patients (≥30 years old) aged 15 to 79 years. The patients were grouped into younger T1DM (n=281), LADY (n=130), younger T2DM (n=200), older T1DM (n=287), LADA (n=129), and older T2DM (n=200) groups. Autoantibodies against thyroid peroxidase (TPOA) and thyroglobulin (TGA) prevalence were analyzed in each group. Results: The prevalence of TGA or TPOA in LADY patients was similar to that in younger T1DM patients. The seropositive rate of TPOA in LADY patients was higher than that in LADA patients (36.2% vs. 23.3%, respectively; P=0.023); the risk of TPOA was higher in LADY patients than in LADA patients, even after adjusting for sex, glutamic acid decarboxylase (GADA)- and insulinoma-associated-2 (IA-2A)-positivity (OR =1.94, P=0.023). LADY patients with high GADA titers exhibited a higher frequency of thyroid autoantibodies than patients with low GADA titers did (TPOA, P=0.005; TGA, P=0.023; TPOA or TGA, P=0.004). Further analysis showed that only male patients showed a strong association between high GADA titers and thyroid autoantibodies positivity, and the association remained significant after adjustment for age (OR =11.14, P=0.025 for TGA; OR =4.99, P=0.011 for TPOA; OR =5.52, P=0.007 for TPOA or TGA). Conclusions: Routine screening for thyroid autoantibodies is recommended in LADY patients, and special clinical attention should be paid to the thyroid autoantibodies status of male patients of LADY with high GADA titers to identify patients at high risk of developing AITD.
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AIMS: To conduct a systematic review and network meta-analysis to determine the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetic kidney disease (DKD). METHODS: Phase III or IV randomized, placebo-controlled trials evaluating SGLT2 inhibitors, GLP-1RAs or DPP-4 inhibitors in patients with DKD were identified from the MEDLINE database. The outcomes of interest were a kidney-specific composite outcome, kidney disease progression, major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF) and cardiovascular death. A network meta-analysis was conducted to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Sixteen trials representing a total of 46 292 patients were included. SGLT2 inhibitors significantly reduced the risk of the kidney-specific composite outcome by 26% compared to GLP-1RAs (HR 0.74, 95% CI 0.62-0.88) and by 36% compared to DPP-4 inhibitors (HR 0.64, 95% CI 0.52-0.79). The risk of MACE was significantly reduced with SGLT2 inhibitors (by 18%; HR 0.82, 95% CI 0.72-0.93), and with GLP-1RAs (by 18%; HR 0.82, 95% CI 0.69-0.96), compared to DPP-4 inhibitors. SGLT2 inhibitors significantly reduced the risk of HHF by 28% compared to GLP-1RAs (HR 0.72, 95% CI 0.56-0.92) and by 41% compared to DPP-4 inhibitors (HR 0.59, 95% CI 0.49-0.71). CONCLUSIONS: A clear advantage was demonstrated by SGLT2 inhibitors in reducing the risks of CV and renal events in patients with DKD, compared to GLP-1RAs and DPP-4 inhibitors. We recommend that SGLT2 inhibitors be considered the treatment of choice in patients with DKD.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Inhibidores de la Dipeptidil-Peptidasa IV , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/inducido químicamente , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/prevención & control , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Humanos , Hipoglucemiantes/uso terapéutico , Riñón , Metaanálisis en Red , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
Epitope-specific GAD65Abs and HLA-DR-DQ gene assays help improve the value of risk stratification in autoimmune diabetes mellitus and protect islet function. Identification and early intervention are important for latent autoimmune diabetes in youth (LADY). The aims of this study were to investigate 1) the frequencies of the epitope-specific GAD65Abs and HLA-DR-DQ genes in LADY and 2) the association between HLA-DR-DQ genes and epitope-specific GAD65Abs. Higher frequencies of GAD65-CAb and multiepitope GAD65Abs were observed in young type 1 diabetes, LADY, and old type 1 diabetes subjects than those in latent autoimmune diabetes in adult (LADA) patients. The frequencies of the specific susceptible HLA haplotype DR3, total susceptible HLA haplotypes, and high-risk genotypes were higher in type 1 diabetes and LADY patients than those in LADA patients. In contrast, type 1 diabetes and LADY patients had lower frequencies of low/no genetic risk genotypes (DRX/X) than those of LADA patients. Logistic regression analysis suggested that the susceptible HLA haplotypes were risk factors for glutamic acid decarboxylase antibody (GADA) multiepitope positivity in autoimmune diabetes mellitus. LADY may be more severe than LADA, and LADY seemed to be a transitional type of type 1 diabetes and LADA. GADA epitope and HLA-DR-DQ gene assays are important for risk stratification in autoimmune diabetes mellitus and protection of islet function.
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Diabetes Mellitus Tipo 1 , Intolerancia a la Glucosa , Adolescente , Adulto , Autoanticuerpos , Diabetes Mellitus Tipo 1/genética , Epítopos/genética , Antecedentes Genéticos , Antígeno HLA-DR3/genética , HumanosRESUMEN
PURPOSE: Metabolic syndrome (Mets) is a pathological condition that includes many abnormal metabolic components and requires a simple detection method for rapid use in a large population. The aim of the study was to develop a diagnostic model for Mets in a Chinese population with noninvasive anthropometric and demographic predictors. PATIENTS AND METHODS: Least absolute shrinkage and selection operator (LASSO) regression was used to screen predictors. A large sample from the China National Diabetes and Metabolic Disorders Survey (CNDMDS) was used to develop the model with logistic regression, and internal, internal-external and external validation were conducted to evaluate the model performance. A score calculator was developed to display the final model. RESULTS: We evaluated the discrimination and calibration of the model by receiver operator characteristic (ROC) curves and calibration curve analysis. The area under the ROC curves (AUCs) and the Brier score of the original model were 0.88 and 0.122, respectively. The mean AUCs and the mean Brier score of 10-fold cross validation were 0.879 and 0.122, respectively. The mean AUCs and the mean Brier score of internal-external validation were 0.878 and 0.121, respectively. The AUCs and Brier score of external validation were 0.862 and 0.133, respectively. CONCLUSIONS: The model developed in this study has good discrimination and calibration performance. Its stability was proved by internal validation, external validation and internal-external validation. Then, this model has been displayed by a calculator which can exhibit the specific predictive probability for easy use in Chinese population.
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Antropometría/métodos , Síndrome Metabólico/diagnóstico , Glucemia/análisis , China/epidemiología , HDL-Colesterol/sangre , Demografía , Ayuno , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Modelos Estadísticos , Obesidad Abdominal/epidemiología , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los Resultados , Triglicéridos/sangreRESUMEN
AIMS: To demonstrate the noninferiority of alogliptin to acarbose, in terms of antidiabetic efficacy, in Chinese people with uncontrolled type 2 diabetes (T2D) and high cardiovascular risk. MATERIALS AND METHODS: ACADEMIC (NCT03794336) was a randomized, open-label, phase IV study conducted at 46 sites in China. Antidiabetic treatment-naive or metformin-treated adults with uncontrolled T2D (glycated haemoglobin [HbA1c] 58.0-97.0 mmol/mol) were randomized 2:1 to alogliptin 25 mg once daily or acarbose 100 mg three times daily for 16 weeks. All participants had a documented history of coronary heart disease or high cardiovascular risk at screening and received aspirin (acetylsalicylic acid) 100 mg daily throughout the trial. The primary endpoints were change in HbA1c versus baseline, and the incidence of gastrointestinal adverse events (AEs). Safety and tolerability were also assessed. RESULTS: A total of 1088 participants were randomized. Alogliptin was noninferior to acarbose for the change in Week-16 HbA1c (least-squares mean change [standard error] -11.9 [0.4] vs. -11.4 [0.5] mmol/mol, respectively; difference between arms -0.5 [0.7] mmol/mol; 95% confidence interval -1.9 to 0.8 mmol/mol), and was associated with a lower incidence of gastrointestinal AEs (8.9% vs. 33.6%, respectively; P < 0.0001). More alogliptin than acarbose recipients achieved HbA1c <53.0 mmol/mol without gastrointestinal AEs (48.0% vs. 32.7%; P < 0.0001). Discontinuations due to treatment-related AEs were less frequent with alogliptin than acarbose (0.3% vs. 2.5%). CONCLUSIONS: Glycaemic control was comparable between alogliptin and acarbose, but the gastrointestinal tolerability of alogliptin was better. More patients achieved target HbA1c without gastrointestinal AEs with alogliptin, suggesting that this agent may be preferred in clinical practice.
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Acarbosa , Diabetes Mellitus Tipo 2 , Piperidinas , Uracilo , Acarbosa/efectos adversos , Adulto , Aspirina/uso terapéutico , Enfermedad Coronaria/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Método Doble Ciego , Hemoglobina Glucada , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hipoglucemiantes/efectos adversos , Metformina/uso terapéutico , Piperidinas/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Uracilo/efectos adversos , Uracilo/análogos & derivadosRESUMEN
Background: The detection of islet autoantibodies is essential for the accurate classification and diagnosis of diabetes mellitus (DM). The islet autoantibody distribution varies by age. However, screening strategies for DM patients with different onset ages remain lacking. Materials and Methods: This cross-sectional study included 17,536 DM patients from 46 medical centers across China. The seroprevalence of glutamic acid decarboxylase autoantibody (GADA), insulinoma-associated-2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A), and insulin autoantibody (IAA) was determined in younger and older patients with type 1 DM (T1DM) (n = 287 and 285, respectively), younger and older patients with latent autoimmune diabetes (LAD) (n = 140 and 121, respectively), and younger and older patients with type 2 DM (n = 200 in each group). Results: The cutoff age between younger and older patients was 35 years using restricted cubic spline method (n = 17,536, adjusted R2 = 0.97, residual standard error = 1.32; P < 0.001). The seroprevalence rates of four islet autoantibodies were higher in patients aged 15-35 years than in those ≥35 years (GADA: 17% vs. 5.6%, IA-2A: 8.5% vs. 1.3%, ZnT8A: 6.3% vs. 2.3%, IAA: 2.2% vs. 1.0%). The prevalence of ZnT8A was higher in LAD patients than in T1DM patients, especially in older LAD patients. The results indicated that ZnT8A detection can increase the detection rate of older LAD patients from 70.2% (based on GADA detection alone) to 91.7%. Conclusions: In patients stratified according to the cutoff age of 35 years, the optimal detection sequence should be GADA, IA-2A, and ZnT8A in younger patients and GADA, ZnT8A, and IA-2A in older patients, so as to reduce the screening cost while improving the detection rate. Particularly, the ZnT8A test is recommended in older patients to avoid a missed LAD diagnosis.
Asunto(s)
Autoanticuerpos/aislamiento & purificación , Diabetes Mellitus Tipo 1 , Adolescente , Adulto , Proteínas de Transporte de Catión , Estudios Transversales , Diabetes Mellitus Tipo 1/diagnóstico , Glutamato Descarboxilasa , Humanos , Estudios Seroepidemiológicos , Adulto Joven , Transportador 8 de ZincRESUMEN
AIMS: Glycated albumin (GA) is a biomarker for short-term (2-3 weeks) glycaemic control. However, the predictive utility of GA for diabetes and prediabetes is largely uncharacterised. We aimed to investigate the relationships of baseline serum GA levels with incident diabetes and prediabetes. METHODS: This was a longitudinal cohort study involving 516 subjects without diabetes or prediabetes at baseline. Blood glucose levels were observed during follow-up. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using COX proportional hazard models. Receiver operating characteristic curves and areas under the curves (AUCs) were used to evaluate the discriminating abilities of glycaemic biomarkers and prediction models. RESULTS: During a 9-year follow-up, 51 individuals (9.88%) developed diabetes and 92 (17.83%) prediabetes. Unadjusted HRs (95% CI) for both diabetes and prediabetes increased proportionally with increasing GA levels in a dose-response manner. Multivariable-adjusted HRs (95% CI) for diabetes were significantly elevated from 1.0 (reference) to 5.58 (1.86-16.74). However, the trend was no longer significant for prediabetes after multivariable adjustment. AUCs for GA, fasting blood glucose (FBG) and 2-h postprandial blood glucose (2h-PBG) for predicting diabetes were 0.698, 0.655 and 0.725, respectively. The AUCs for GA had no significant differences compared with those for FBG (p = 0.376) and 2h-PBG (p = 0.552). Replacing FBG or 2h-PBG or both with GA in diabetes prediction models made no significant changes to the AUCs of the models. CONCLUSIONS: GA is of good prognostic utility in predicting diabetes. However, GA may not be a useful biomarker for predicting prediabetes.
Asunto(s)
Diabetes Mellitus Tipo 2 , Estado Prediabético , Biomarcadores , Glucemia , Estudios de Cohortes , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Hemoglobina Glucada/análisis , Productos Finales de Glicación Avanzada , Humanos , Estudios Longitudinales , Estado Prediabético/diagnóstico , Estado Prediabético/epidemiología , Estudios Retrospectivos , Albúmina Sérica , Albúmina Sérica GlicadaRESUMEN
MATERIALS AND METHODS: We screened four databases (PubMed, Embase, Cochran Library, and CNKI) for the observational studies about the OSA and T2DM. Studies were collected from database establishment to October 2020. We performed a traditional subgroup meta-analysis. What is more, linear and spline dose-response models were applied to assess the association between apnea-hypopnea index (AHI), an indicator to evaluate the severity of OSA, and the risk of T2DM. Review Manager, version 5.3, software and Stata 16.0 were used for the analysis. RESULT: Seven observational studies were included in the research. We excluded a study in the conventional meta-analysis. In the subgroup analysis, mild-dose AHI increased the risk of T2DM (odds ratio = 1.23, 95% confidence interval = 1.06-1.41, P < 0.05). Moderate-dose AHI increased the risk of T2DM with a higher odds ratio (OR = 1.35, 95% CI = 1.13-1.61, P < 0.05). Moderate-to-severe-dose AHI increased the risk of T2DM with a higher odds ratio (OR = 2.14, 95% CI = 1.72-2.67, P < 0.05). Severe-dose AHI increased the risk of T2DM with a higher odds ratio (OR = 2.19 95% CI = 1.30-3.68, P < 0.05). Furthermore, the spline and linear dose-response meta-analysis results revealed that the risk of T2DM increased with increasing AHI values. CONCLUSION: Through the dose-response meta-analysis, we found a potential dose-response relationship existed between the severity of OSA and the risk of T2DM. This relationship in our passage should be considered in the prevention of T2DM in the future.
RESUMEN
BACKGROUND: Berberine and Bifidobacterium have been reported to improve glucose tolerance in people with hyperglycemia or other metabolic disorders. This study aimed to assess the hypoglycemic effect and the regulation of the gut microbiota caused by berberine and Bifidobacterium and the possible additive benefits of their combination. METHODS: This was an 18-week, multi-center, randomized, double-blind, parallel-controlled study of patients newly diagnosed with hyperglycemia. After a 2-week run-in period, 300 participants were randomly assigned to the following four groups for 16 weeks of treatment: berberine (Be), Bifidobacterium (Bi), berberine and Bifidobacterium (BB), and placebo group. The primary efficacy endpoint was the absolute value of fasting plasma glucose (FPG) compared with baseline after 16 weeks of treatment. RESULTS: Between October 2015 and April 2018, a total of 297 participants were included in the primary analysis. Significant reductions of FPG were observed in the Be and BB groups compared with the placebo group, with a least square (LS) mean difference of - 0.50, 95% CI [- 0.85, - 0.15] mmol/L, and - 0.55, 95% CI [- 0.91, - 0.20] mmol/L, respectively. The Be and BB groups also showed significant reductions in 2-h postprandial plasma glucose. A pronounced decrease in HbA1c occurred in the BB group compared to the placebo group. Moreover, compared with the Bi and placebo groups, the Be and BB groups had more changes in the gut microbiota from the baseline. CONCLUSIONS: Berberine could regulate the structure and function of the human gut microbiota, and Bifidobacterium has the potential to enhance the hypoglycemic effect of berberine. These findings provide new insights into the hypoglycemic potential of berberine and Bifidobacterium. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03330184. Retrospectively registered on 18 October 2017.